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Role of the septohippocampal GABAergic system in spatial orientation

Koppen JR, Winter SS, Cheatwood JL, Wallace DG (2010) Role of the septohippocampal GABAergic system in spatial orientation. Neuroscience 2010 Abstracts 806.16/KKK21. Society for Neuroscience, San Diego, CA.

Summary: Spatial orientation depends on the integrity of multiple neural systems. For example, during the progression of Alzheimer’s Disease, degeneration of the basal forebrain is associated with cognitive impairments including episodes of wandering. The medial septum projects both cholinergic and GABAergic fibers into the hippocampus. Research and therapies have typically focused on enhancing function of the cholinergic component; however, the GABAergic component has also been shown to contribute to hippocampal function. Previous attempts to characterize the role of the GABAergic system in spatial orientation involved non-selective lesion techniques in combination with the water maze task have failed to characterize the nature of the deficit mediating the impaired performance. Development of GAT1-Saporin immunotoxin provides a novel tool to selectively destroy GABAergic neurons in the medial septum. The current study examined the effects of injecting GAT1-Saporin or saline (sham lesion) into the medial septum on spatial orientation using the food-hoarding paradigm. The food-hoarding paradigm involves training rats to search for food pellets on a large circular table and carrying the food pellet directly to a visible refuge. Three probes dissociate the use of environmental and self-movement cues: 1) Hidden probe involved placing the refuge below the surface of the table, limiting rats to use distal environmental or self-movement cues to locate the refuge; 2) Dark Probe involved using the hidden refuge with the room lights off, limiting rats to use self-movement cues to locate the refuge; 3) New probe involved placing the hidden refuge on the opposite side of table, placing environmental and self-movement cues in conflict. Both sham and GAT1-Saporin rats were accurate in returning to the refuge during the Hidden probe. Only sham rats were accurate in carrying food to the refuge during the Dark probe. During the New probe, both groups initially carried the food pellet to the former refuge location. Although sham rats consistently carried the food pellet to the new refuge location after their initial error, GAT1-Saporin rats continued to perseverate to the former refuge location. The current study demonstrates a role for the septohippocampal GABAergic system in spatial orientation related to processing self-movement cues.

Related Products: GAT1-SAP (Cat. #IT-32)

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